The analysis of human breath samples promises to be a powerful non-invasive diagnostic tool for detecting many diseases, including lung cancer, diabetes, tuberculosis, heart disease, and chronic obstructive pulmonary disease (COPD). Breath is a complex mixture of atmospheric gases, water, and trace volatile organic compounds (VOCs) and nonvolatile compounds. The VOCs in breath are generally assumed to derive mainly from blood by passive diffusion across the pulmonary alveolar membrane. Gas chromatography coupled with a mass spectrometer detector (GC-MS) is currently the technique of choice for analysis of VOCs in breath. In 1971, Pauling first reported gas-chromatography (GC) for analysis of breath and his study revealed the presence of large numbers of VOCs in human breath. It is now known that breath contains at least 200 different VOCs that have been proposed as biomarkers for various disease states.
However, some of the critical challenges for breath analysis include that: many of the VOCs in breath range from only a few parts per trillion (ppt) to a few parts per billion (ppb) concentration; many chemical species in breath samples are at millions-fold higher concentration than VOCs, such as water vapor and carbon dioxide, which may need to be removed to avoid swamping most analytical instruments; breath is a very complex mixture containing more than 200 VOCs consisting of diverse mixtures of alcohols, ketones, and aldehydes, which complicates the identification of disease biomarkers; and VOCs in breath include non-metabolic constituents, which may introduce false biomarkers in breath analysis.
Thus, in order to efficiently and accurately analyze VOCs in breath, the first hurdle to overcome is that of concentrating the VOCs of interest. General approaches to concentrating one or more VOCs of interest from dilute gaseous samples have focused on one of the following: chemical, cryogenic, and adsorptive.
Chemical trapping has traditionally used “wet chemistry” where breath is bubbled through a reagent solution that captures a specific compound, such as ethanol or acetone. One disadvantage of the technique is that trace chemical loss is a problem in real breath sample analysis.
For cryogenic trapping, the volatile compounds are captured by condensing or freezing the VOCs in a cold trap. However, a cold trap may also freeze water and carbon dioxide, both of which are abundant in breath, and thus may plug the cold trap.
Adsorptive trapping is generally considered to be the most convenient and thus, the most widely used approach. In this method, VOCs are captured by binding them to adsorbent agents. Various adsorptive materials have been used as adsorbent in breath analysis, such as organic polymers (e.g., Tenax® TA), activated charcoal, graphitized carbon, and carbon molecular sieves (e.g., Carboxen™ 1021).
The majority of existing pre-concentrators trap VOCs by physical adsorption, with resulting low efficiency or speed. Attempts to enhance these physical adsorption pre-concentrators have included invoking high surface area construction, such as stainless steel or glass-capillary tubes packed with one or more granular absorbent materials. Other physical adsorption pre-concentrators have been fabricated on silicon wafers using micro-electromechanical system (MEMS) technology, which typically employ a micro-hotplate and an adsorption material layer deposited on the active area adjacent to the heating element. However, even these pre-concentrators have common physical adsorption efficiency and selectivity problems.
Further, a problem inherent to the physical adsorption methodology is that any increase in the efficiency of the adsorption step generally results in a lowered efficiency of the thermal desorption step to subsequently release the trapped VOCs. In view thereof, a need exists for new pre-concentrators to overcome the challenges of the prior art.